الفهرس 
Skeletal muscle atrophyOnly 14 pages are availabe for public view
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Abstract
Skeletal muscle atrophy is defined as loss of the muscle mass due to imbalance between protein synthesis and degradation in response to various conditions and results in muscle weakness which limits activity and impairs quality of life. Glucocorticoid-induced atrophy is the most common type of drug-induced myopathy and can be induced by both natural and synthetic glucocorticoid preparations specially when used chronically, also from increased endogenous secretion. It results from activation of catabolic pathways and suppression of anabolic pathways controlling protein synthesis. Oxidative stress and apoptosis are important causes in the pathophysiology of glucocorticoid-induced atrophy. Lowering of testosterone level by dexamethasone plays a role too. The resulting muscle atrophy is characterized by body weight loss, muscle weight loss, muscle weakness, and fatigue which limit their clinical use. Dexamethasone, a synthetic, fluorinated glucocorticoid, exerts a major direct action on protein turnover in isolated muscles, compared with naturally secreted hormones. It is characterized by long action and minimal mineralocorticoid activity. Dexamethasone was administered in a dose of 2mg/kg/day S.C., for 14 days, this dose was selected depending on results from previous studies. Luteolin, a flavonoid present in edible plants, is characterized by multiple biochemical and biological activities, For instance, luteolin is antioxidant, antiapoptotic, phosphodiesterase inhibitor, and aromatase inhibitor. These biological effects makes luteolin an attracting agent to be tested in different disease conditions. Its effect was tested in lipopolysaccharide induced myotubes’ atrophy, and it was proven that it has anti-atrophic effect. In the present study, anti-atrophic effect of luteolin was investigated for the first time in vivo in dexamethasone induced skeletal muscle atrophy in albino rats. The study was started using 60 rats equally divided randomly into 5 groups (12 rats for each group). Experiment was completed where a total of 14 rats died through the experiment (2 rats from Dex group, 4 rats from group Lut 25, 4 rats from group Lut 50 and 4 rats from group Lut 100), were excluded with a final selection of 40 rats (8 rats for each group). The design of the groups was as follows: - group 1 (Control): rats received a vehicle of CMC 0.5% daily orally and Saline injection subcutaneously daily and served as normal control group. - group 2 (Dex): rats received dexamethasone in a dose of 2 mg/kg/day for 2 weeks by S.C. injection to induce muscle atrophy and received a vehicle of CMC 0.5% daily by oral gavage and served as untreated diseased group. - group 3 (Lut 25): rats with dexamethasone induced muscle atrophy were treated by luteolin administered by oral gavage in a low dose of 25 mg/kg/day - group 4 (Lut 50): rats with dexamethasone induced muscle atrophy diseased group were treated by luteolin administered by oral gavage in an intermediate dose of 50 mg/kg/day. - group 5 (Lut 100): rats with dexamethasone induced muscle atrophy diseased group were treated by luteolin administered by oral gavage in a high dose of 100 mg/kg/day. Luteolin treatment with different doses 25, 50, 100 mg/kg/day was started from first day concomitant with dexamethasone injection till end of the experiment at day 14. Body weight of rats was recorded at the start and the end of the experiment, muscle strength was assessed by hanging wire test at day 13. At day 15, animals were sacrificed, blood collected by cardiac puncture, centrifuged, and serum was collected and stored for measurement of: • Serum testosterone levels • Serum creatine kinase activity Gastrocnemius muscles were dissected and muscle weight was recorded. Right muscle was homogenized for measurement of: • Reduced glutathione (GSH) levels. • Malondialdehyde (MDA) levels. • Cyclic adenosine monophosphate (cAMP) levels. - Left gastrocnemius muscle was stored in formalin 10% for • Histological examination and fiber cross sectional area (CSA) measurement • Immunohistochemical expression of caspase-3.